Diabetes and cancer are common diseases that have a tremendous impact on health worldwide. A number of studies have indicated that diabetes is associated with higher overall mortality in patients with breast cancer. However, it is unclear whether the higher overall mortality seen in breast cancer patients with diabetes compared to those without diabetes is related to a poorer breast cancer prognosis, to other causes such as cardiovascular disease, or to different management of breast cancer, including tumor characteristics and treatment choices. In addition, metformin, an oral drug widely used as a first-line therapy for type 2 diabetes, is also under consideration for use in non-diabetic cancer patients as an adjunctive therapy. However, there is no study examining its potential effect on cancer prognosis in a population-based setting. Answering these questions will have direct influence on diabetes management and cancer treatment to improve breast cancer outcomes for women with diabetes and is critical to inform the proper care of these patients. We will use data from the Women's Health Initiative (WHI), a large prospective cohort study, to assess influence of pre-existing diabetes (specific aim 1) and diabetes treatment, particularly metformin (specific aim 2), on prognosis of patients with breast cancer. This is the first prospective study o use a well-established cohort to address these questions. The Women's Health Initiative includes detailed and comprehensive data on demographic and psychosocial characteristics, breast cancer screening, breast cancer risk factors, diabetes medication treatments, tumor characteristics that are physician-adjudicated and coded using SEER protocols and physician-adjudicated causes of death. We expect the proposed analyses to advance understanding of whether and how pre-existing diabetes and diabetes treatment influences survival following breast cancer. In addition, the novel analyses and methods used for this study can be expanded in the future to a more comprehensive examination of other types of cancer in relation to diabetes or other co-morbidities. Additionally, this project will provide great opportunities for exposing students to research and stimulating their interests in pursuing careers in academic fields.